Tumor is a neoplasma formed in the organism under various oncogenic factors, bringing about the change in the cell genetic material, and leading to the abnormal gene expression and the cell abnormal proliferation. Tumor cells lose the normal growth regulation function, has an autonomic or a relative autonomic growth capability. Even if the oncogenic factor disappears, the tumor cells can continue to grow and consume a large amount of nutrient substances in the human body. If finding and treating the tumor is not prompt, the tumor cells may also transfer to various places in the whole body to grow and propagate, and release many toxins, leading to maransis, anaemia, organ function impairment and even the death of the human being.
The therapy for treating tumor mainly comprises the following three aspects: medicament therapy, surgical therapy and radiation therapy. Since it is difficult for the surgical therapy and the radiation therapy to eradicate the tumor thoroughly, and the surgical therapy and the radiation therapy have little function to the patients in the middle-late stage, therefore the medicament therapy becomes more and more important in the tumor treatment. Traditional antineoplastic drug cannot distinguish the tumor cells from the normal tissue cells, leading to a severe side effect. The targeted drug aims at the cancer cells as the specific target, can accurately target to the tumor, and accordingly improves the therapeutic level greatly and decreases the adverse effect ratio. For example, it can increase the median live time for the late-stage large intestine carcinoma by 66.7%, and the treatment effective rate for the late-stage mammary cancer by 71.3%.
Because many pharmaceuticals company has accelerated the research and development in the targeted antineoplastic drug, plus because there is a strong requirement on this kind of the antineoplastic drug in the commercial market, the molecular targeted drug has became a fastest growth unit in the global antineoplastic drug market. PI3K pathway is a place where the human tumor cells are subjected to variation most frequently, which may lead to the cell proliferation, activation, and amplification of signal. Phosphatidylinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) are the most important kinases for the PI3K signaling pathway.
Phosphatidylinositol-3-kinase (PI3K) refers to a member of the lipid kinase family, which can produce the phosphatidylinositol 3-phosphate (PIP3) through the 3-position phosphorylation of phosphatidylinositol to regulate the cell metabolism and growth. The second messenger PIP3 of this kind may cause the PI3K and the downstream effector (in particular AKt) to combine in pair, leading to membrane recruitment and phosphorylation, cell proliferation and activation. Therefore, the inhibition of Phosphatidylinositol-3-kinase may have an influence on the PI3K pathway, and accordingly inhibit the cancer cell proliferation and activation.
The mTOR is a serine/threonine protein kinase present in kytoplasm, belongs to phosphoinositide kinase dependent protein kinase family, and present in the organism in a form of two complexes, i.e. mTORC1 (the target point for rapamycin) and mTORC2 (not inhibited by rapamycin). The mTOR is a cell signal transducer. It regulates the response of the tumor cells to the nutrients and growth factors, and controls the blood supply to the tumor through the effect on vascular endothelial growth factor. The mTOR inhibitor can make the tumor cells starve and inhibit the mTOR, leading to the decrease in the tumor volume.
Currently, there is some drug development in the dual PI3K and mTOR inhibitor. However, most of such compounds have poor druggability, and this kind of compounds has not entered the pharmaceutical market. Journal of Medicinal Chemistry (2011), 54(5), 1473-1480, “Discovery of 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one (Torin2) as a potent, selective, and orally available mammalian target of rapamycin (mTOR) inhibitor for treatment of cancer” discloses a compound named Torin2 and reports the research results on its in vivo pharmacokinetics.

In summary, it has became hot in the current research for the antineoplastic drug to seek a compound having a dual PI3K and mTOR inhibition, a good activity, a high selectivity, and a good pharmacokinetic characteristics.
The present inventors, upon developing the drug with the good antineoplastic effect, have found a class of pyridonaphthyridine compound having a dual PI3K and mTOR inhibition.